Biological analysis system and methods

ABSTRACT

A system for biological analysis includes a housing, a block assembly within the housing having a sample block and a baseplate, a heated cover and a cover carrier. The sample block receives a sample holder comprising an RFID tag. A first drive mechanism generates relative movement between the sample block and the baseplate along a first axis. A second drive mechanism generates relative movement between the heated cover and the cover carrier along a second axis that is different from the first axis. Based on a first command the first drive mechanism releasably engages the sample block and operates the second drive mechanism to releasably engage the heated cover with the cover carrier. The system also includes first and second RFID antennas that receive RFID data from the sample holder RFID tag that is read by at least one RFID reader.

FIELD OF THE DISCLOSURE

The present disclosure relates broadly, but not exclusively, tobiological analysis systems and related methods, including polymerasechain reaction (PCR) systems.

BACKGROUND

Biological analysis systems, such as PCR systems, are useful tools forconducting diagnostics and research in biological or biochemicalsamples. A PCR system typically has a thermal cycler that heats andcools the samples over a number of cycles to achieve the desiredamplification of one or more target molecules. Real-time PCR systems,also known as qualitative PCR (qPCR) systems allow monitoring of a PCRassay during each thermal cycle of the process.

Generally, there is an increasing need to simplify the installation andsetup of biological analysis systems so that operators can more quicklyand efficiently use biological analysis systems for their intendedpurpose. However, existing systems typically require manual operation orintervention which may result in inefficiency and inconsistency.

Thus, it is desirable to provide a biological analysis system that canaddress at least one of the above problems.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the present disclosure will be better understood andreadily apparent to one of ordinary skill in the art from the followingwritten description, by way of example only, and in conjunction with thedrawings, in which:

FIG. 1 shows a block diagram that illustrates a PCR instrument uponwhich embodiments of the present teachings may be implemented.

FIG. 2 shows a block diagram that illustrates a computer system that maybe employed to carry out processing functionality, according to someexemplary embodiments of the disclosure.

FIGS. 3A-3B show exploded and assembled views, respectively, of a blockassembly according to an example embodiment.

FIGS. 3C-3D show perspective views of sample block and sample holderaccording to an example embodiment.

FIGS. 4A-4B show withdrawn and extended positions, respectively, of theblock assembly of FIGS. 3A-3B according to an example embodiment.

FIGS. 5A-5B show the sample block of the block assembly of FIGS. 3A-3Bin disengaged and engaged states, respectively, with a base according toan example embodiment.

FIGS. 6A-6B shows magnified views of portions of the block assembly ofFIGS. 3A-3B.

FIG. 7 shows a perspective view of an optics assembly having a covercarrier connected thereto according to an example embodiment.

FIGS. 8A-8D show cross-sectional view illustrating an operation of thecover carrier according to an example embodiment.

FIGS. 9A-9H and 9J-9K show various views a cover carrier according to anexample embodiment.

FIGS. 10A-10B show exploded and assembled views, respective, of abiological analysis system according to an example embodiment and areagent with RFID tag.

FIGS. 11A-11B show close-up cross-sectional views inside the assembledsystem of FIGS. 10A-10B according to an example embodiment.

FIG. 12 shows a partial cross-sectional view of the assembled system ofFIGS. 10A-10B according to an example embodiment.

FIG. 13 shows a flow diagram of a method accord to an exampleembodiment.

FIG. 14 shows a flow diagram of a method accord to an exampleembodiment.

FIG. 15 shows a flow diagram of a method accord to an exampleembodiment.

DETAILED DESCRIPTION

To provide a more thorough understanding of the present disclosure, thefollowing description sets forth numerous specific details, such asspecific configurations, parameters, examples, and the like. It shouldbe recognized, however, that such description is not intended as alimitation on the scope of the present invention, but is intended toprovide a better description of the exemplary embodiments.

It should also be recognized that the methods and systems describedherein may be implemented in various types of systems, instruments, andmachines such as biological analysis systems. For example, variousembodiments may be implemented in an instrument, system or machine thatperforms polymerase chain reactions (PCR) on a plurality of samples.While generally applicable to quantitative polymerase chain reactions(qPCR) where a large number of samples are being processed, it should berecognized that any suitable PCR method may be used in accordance withvarious embodiments described herein. Suitable PCR methods include, butare not limited to, digital PCR, allele-specific PCR, asymmetric PCR,ligation-mediated PCR, multiplex PCR, nested PCR, qPCR, genome walking,and bridge PCR, for example. Furthermore, as used herein, thermalcycling may include using a thermal cycler, isothermal amplification,thermal convection, infrared mediated thermal cycling, or helicasedependent amplification.

The term “radio frequency identifier”, “radio frequency identifier tag”,or “RFID tag” as used herein may refer to a chip comprising anintegrated circuit and an antenna. The integrated circuitry may storedata that can be communicated by a radio frequency transmitted by theantenna. The integrated circuit and antenna circuitry may be printed onthe chip. An RFID “tag” or “transponder” can be read by an RFID readerusing an antenna that emits radio frequencies to query the transponder.A “passive RFID” does not have its own energy source, but responds tosignals from a reader to transmit a signal. An “active RFID” includes abattery as a power source. Some examples of RFID tags can be found inU.S. Pat. Nos. 6,147,662; 6,917,291; 5,949,049; 6,652,812; 6,112,152;and U.S. Pat. Application No. 2003/0183683 all of which are hereinincorporated by reference in their entireties for their disclosure ofRFID tags, chips, labels, or devices, RFID readers, and RFID systems,their design and use. A “writable radio frequency identifier” or“writable RFID” is an RFID tag that has memory space that can be writtento by an RFID writer.

The term “sample holder” as used herein may refer to a structure fordirectly or indirectly supporting one or more reaction sites, eachconfigured to contain a biological sample and any associated reagents,dyes, probes, detergents, enzymes, master mixes, or the like. Examplesof sample holders include, but are not limited to, reaction plates,tubes, tube carriers, surface plasmon resonance arrays, slides, conicallow-volume tubes, microfluidic cards, microarray chips, plates orcartridges, through-hole arrays, sample preparation devices, assaypreparation devices, electrophoretic type device, electroosmotic typedevices, immunoassays, combinatorial libraries, molecular libraries,phage display libraries, DNA libraries, DNA fingerprinting devices, SNPdetection devices, vacuum containers, and other types of containers forsupporting biological reagents or assays. The sample holder can be amulti-well tray or microtiter plate including, for example, 4, 12, 24,48, 96, 192, 384, 768, 1536, 3072, 6144, 12288, or more wells or sampleretainment regions. The sample holder can retain a fluid, if the sampleholder can be utilized to transfer, contain, encompass, or otherwisehold, permanently or temporarily, a fluid. The sample holder materialcan comprise any materials used in chemical and biochemical synthesis.The sample holder material can comprise polymeric materials that arecompatible with chemical and biological syntheses and assays, andinclude glasses, silicates, celluloses, polystyrenes, polysaccharides,sand, and synthetic resins and polymers, including acrylamides,particularly cross-linked polymers, cotton, and other such materials.The sample holder material can be in the form of particles or can becontinuous in design, such as a test tube or microtiter plate or thelike.

As used herein, the terms “communication”, “electrical communication”,or “electronic communication” generally means communication between twoor more electronic components (e.g., electronic devices or electronicsystems). The communication may be achieved via a physical connectionbetween (e.g., an electrical wire, an electrical cable, fiber opticcable, or the like connected to both two electronic components or via athird electronic component to which first and second communicatingcomponents are commonly connected, for example, a network system such asa Local Area Network (LAN), or a wide area network (WAN), or the like).Additionally or alternatively, the electrical communication may be via atransmitter/receiver configuration, for example, a direct wirelesscommunication between the devices (e.g., between antennas in twocommunicating components, a Bluetooth connection, and/or the like) orvia wireless network (e.g., a wireless router system, Wi-Fi connection,or wireless data communication system, such as provided by atelecommunications provider). The electrical communication mayadditionally or alternatively be provided via communication of thedevice to a common database, such as a Cloud database.

System Overview

As mentioned above, an instrument according to embodiments of thepresent teaching may be utilized to perform various types of biologicalassays, experiments, tests, or the like. In the current disclosure,embodiments of an instrument for use in conducting polymerase chainreaction (PCR) assays are illustrated using a microtiter plate. However,embodiments of the present teaching extend to other types of instruments(e.g. capillary electrophoresis instruments, sequencing instruments,such as Next Generation Sequencing (NGS) instruments, microarraysystems, flow cytometers, and the like), sample holders (e.g., asdiscussed above herein), and assays such (e.g., capillaryelectrophoresis, genetic sequencing, genotyping, and the like).

FIG. 1 shows a block diagram that illustrates elements of an instrument100, such as a Real-time PCR instrument 100, upon which embodiments ofthe present teachings may be implemented. Real-time PCR instrument 100may include a heated cover 110 that is placed over a plurality ofsamples 112 contained in a substrate, plate, or sample holder (not shownhere). In various embodiments, a sample holder may be a glass or plasticslide with a plurality of sample regions, which sample regions have acover between the sample regions and heated cover 110. The sample holdermay comprise one or more reaction sites in various embodiments, whichmay include depressions, wells, through-holes, indentations, surfacediscontinuities, ridges, and combinations thereof, which may bepatterned in regular or irregular arrays formed on the surface of thesample holder. The PCR instrument also includes a sample block 114 forholding or maintaining a plurality of samples and a thermal block 116for heating and/or cooling the sample block 114 and the samplescontained therein. Blocks 114 and 116 may be coupled or connectedtogether to from an integral sample block or sample block assembly 114.

Real-time PCR instrument 100 has an optical system 124. In FIG. 1 , theoptical system 124 may have an illumination source (not shown) thatemits electromagnetic energy, an optical sensor, detector, or imager(not shown), for receiving electromagnetic energy from samples 112 in asample holder, and optics 140 used to guide the electromagnetic energyfrom each DNA sample to the imager. For embodiments of PCR instrument /real-time PCR instrument 100 in FIG. 1 , control system 120 may be usedto control the functions of the detection system, heated cover, andthermal block. Control system 120 may be accessible to an end userthrough user interface 122 of PCR instrument / real-time PCR instrument100 in FIG. 1 . Also a computer system 100, as depicted in FIG. 2 , mayserve as to provide the control the function of PCR instrument 100 inFIG. 1 , as well as the user interface function. Additionally, computersystem 200 of FIG. 2 may provide data processing, display and reportpreparation functions. All such instrument control functions may bededicated locally to the PCR instrument, or computer system 200 of FIG.2 may provide remote control of part or all of the control, analysis,and reporting functions, as will be discussed in more detailsubsequently.

Computer-Implemented System

Methods in accordance with embodiments described herein may beimplemented using a computer system.

Those skilled in the art will recognize that the operations of thevarious embodiments may be implemented using hardware, software,firmware, or combinations thereof, as appropriate. For example, someprocesses can be carried out using processors or other digital circuitryunder the control of software, firmware, or hard-wired logic. (The term“logic” herein refers to fixed hardware, programmable logic and/or anappropriate combination thereof, as would be recognized by one skilledin the art to carry out the recited functions.) Software and firmwarecan be stored on non-transitory computer-readable media. Some otherprocesses can be implemented using analog circuitry, as is well known toone of ordinary skill in the art. Additionally, memory or other storage,as well as communication components, may be employed in embodiments ofthe invention.

FIG. 2 shows a block diagram that illustrates a computer system 200 thatmay be employed to carry out processing functionality, according tovarious embodiments. Instruments to perform experiments may be connectedto the exemplary computing system 200. Computing system 200 can includeone or more processors, such as a processor 204. Processor 204 can beimplemented using a general or special purpose processing engine suchas, for example, a microprocessor, controller or other control logic. Inthis example, processor 204 is connected to a bus 202 or othercommunication medium.

Further, it should be appreciated that a computing system 200 of FIG. 2may be embodied in any of a number of forms, such as a rack-mountedcomputer, mainframe, supercomputer, server, client, a desktop computer,a laptop computer, a tablet computer, hand-held computing device (e.g.,PDA, cell phone, smart phone, palmtop, etc.), cluster grid, netbook,embedded systems, or any other type of special or general purposecomputing device as may be desirable or appropriate for a givenapplication or environment. Additionally, a computing system 200 caninclude a conventional network system including a client/serverenvironment and one or more database servers, or integration withLIS/LIMS infrastructure. A number of conventional network systems,including a local area network (LAN) or a wide area network (WAN), andincluding wireless and/or wired components, are known in the art.Additionally, client/server environments, database servers, and networksare well documented in the art. According to various embodimentsdescribed herein, computing system 200 may be configured to connect toone or more servers in a distributed network. Computing system 200 mayreceive information or updates from the distributed network. Computingsystem 200 may also transmit information to be stored within thedistributed network that may be accessed by other clients connected tothe distributed network.

Computing system 200 may include bus 202 or other communicationmechanism for communicating information, and processor 204 coupled withbus 202 for processing information.

Computing system 200 also includes a memory 206, which can be a randomaccess memory (RAM) or other dynamic memory, coupled to bus 202 forstoring instructions to be executed by processor 204. Memory 206 alsomay be used for storing temporary variables or other intermediateinformation during execution of instructions to be executed by processor204. Computing system 200 further includes a read only memory (ROM) 208or other static storage device coupled to bus 202 for storing staticinformation and instructions for processor 204.

Computing system 200 may also include a storage device 210, such as amagnetic disk, optical disk, or solid state drive (SSD) is provided andcoupled to bus 202 for storing information and instructions. Storagedevice 210 may include a media drive and a removable storage interface.A media drive may include a drive or other mechanism to support fixed orremovable storage media, such as a hard disk drive, a floppy disk drive,a magnetic tape drive, an optical disk drive, a CD or DVD drive (R orRW), flash drive, or other removable or fixed media drive. As theseexamples illustrate, the storage media may include a computer-readablestorage medium having stored therein particular computer software,instructions, or data.

In alternative embodiments, storage device 210 may include other similarinstrumentalities for allowing computer programs or other instructionsor data to be loaded into computing system 200. Such instrumentalitiesmay include, for example, a removable storage unit and an interface,such as a program cartridge and cartridge interface, a removable memory(for example, a flash memory or other removable memory module) andmemory slot, and other removable storage units and interfaces that allowsoftware and data to be transferred from the storage device 210 tocomputing system 200.

Computing system 200 can also include a communications interface 218.Communications interface 218 can be used to allow software and data tobe transferred between computing system 200 and external devices.Examples of communications interface 218 can include a modem, a networkinterface (such as an Ethernet or other NIC card), a communications port(such as for example, a USB port, a RS-232C serial port), a PCMCIA slotand card, Bluetooth, etc. Software and data transferred viacommunications interface 218 are in the form of signals that can beelectronic, electromagnetic, optical or other signals capable of beingreceived by communications interface 218. These signals may betransmitted and received by communications interface 218 via a channelsuch as a wireless medium, wire or cable, fiber optics, or othercommunications medium. Some examples of a channel include a phone line,a cellular phone link, an RF link, a network interface, a local or widearea network, and other communications channels.

Computing system 200 may be coupled via bus 202 to a display 212, suchas a cathode ray tube (CRT) or liquid crystal display (LCD), fordisplaying information to a computer user. An input device 214,including alphanumeric and other keys, is coupled to bus 202 forcommunicating information and command selections to processor 204, forexample. An input device may also be a display, such as an LCD display,configured with touchscreen input capabilities. Another type of userinput device is cursor control 216, such as a mouse, a trackball orcursor direction keys for communicating direction information andcommand selections to processor 204 and for controlling cursor movementon display 212. This input device typically has two degrees of freedomin two axes, a first axis (e.g. x-axis) and a second axis (e.g. y-axis),that allows the device to specify positions in a plane. Computing system200 provides data processing and provides a level of confidence for suchdata. Consistent with certain implementations of embodiments of thepresent teachings, data processing and confidence values are provided bycomputing system 200 in response to processor 204 executing one or moresequences of one or more instructions contained in memory 206. Suchinstructions may be read into memory 206 from another computer-readablemedium, such as storage device 210. Execution of the sequences ofinstructions contained in memory 206 causes processor 204 to perform theprocess states described herein. Alternatively hard-wired circuitry maybe used in place of or in combination with software instructions toimplement embodiments of the present teachings. Thus implementations ofembodiments of the present teachings are not limited to any specificcombination of hardware circuitry and software.

The term “computer-readable medium” and “computer program product” asused herein generally refers to any media that is involved in providingone or more sequences or one or more instructions to processor 204 forexecution. Such instructions, generally referred to as “computer programcode” (which may be grouped in the form of computer programs or othergroupings), when executed, enable the computing system 200 to performfeatures or functions of embodiments of the present invention. These andother forms of non-transitory computer-readable media may take manyforms, including but not limited to, non-volatile media, volatile media,and transmission media. Non-volatile media includes, for example, solidstate, optical or magnetic disks, such as storage device 210. Volatilemedia includes dynamic memory, such as memory 206. Transmission mediaincludes coaxial cables, copper wire, and fiber optics, including thewires that comprise bus 202.

Common forms of computer-readable media include, for example, a floppydisk, a flexible disk, hard disk, magnetic tape, or any other magneticmedium, a CD-ROM, any other optical medium, punch cards, paper tape, anyother physical medium with patterns of holes, a RAM, PROM, and EPROM, aFLASH-EPROM, any other memory chip or cartridge, a carrier wave asdescribed hereinafter, or any other medium from which a computer canread.

Various forms of computer readable media may be involved in carrying oneor more sequences of one or more instructions to processor 204 forexecution. For example, the instructions may initially be carried onmagnetic disk of a remote computer. The remote computer can load theinstructions into its dynamic memory and send the instructions over atelephone line using a modem. A modem local to computing system 200 canreceive the data on the telephone line and use an infra-red transmitterto convert the data to an infra-red signal. An infra-red detectorcoupled to bus 202 can receive the data carried in the infra-red signaland place the data on bus 202. Bus 202 carries the data to memory 206,from which processor 204 retrieves and executes the instructions. Theinstructions received by memory 206 may optionally be stored on storagedevice 210 either before or after execution by processor 204.

It will be appreciated that, for clarity purposes, the above descriptionhas described embodiments of the invention with reference to differentfunctional units and processors. However, it will be apparent that anysuitable distribution of functionality between different functionalunits, processors or domains may be used without detracting from theinvention. For example, functionality illustrated to be performed byseparate processors or controllers may be performed by the sameprocessor or controller. Hence, references to specific functional unitsare only to be seen as references to suitable means for providing thedescribed functionality, rather than indicative of a strict logical orphysical structure or organization.

FIG. 10A shows an exploded perspective view of a biological analysissystem or instrument 1000 according to an example embodiment. FIG. 10Bshows an assembled perspective view of the system 1000 of FIG. 10A. Thesystem 1000 may include a baseplate, frame, or support structure 301 anda housing, enclosure, or case 1001 that is used to house, isolate,and/or protect the various components, assemblies, and subassemblies ofthe system 1000. System 1000 may further comprise a frame 704, which maybe attached, secured, coupled to and/or supported by support structure301. As discussed herein, the system or instrument 1000 compriseselements and systems pertaining to a qPCR system or instrument. However,the scope of the various embodiment disclose herein may cover othertypes of systems or instruments, such as other types of biologicalanalysis systems or instruments, such as those listed above herein.

Referring to FIGS. 3A and 3B, the system 1000 may comprise a blockassembly 300. FIG. 3A shows an exploded perspective view of the blockassembly 300 according to an example embodiment. FIG. 3B shows anassembled perspective view of the block assembly 300 of FIG. 3A. Withadditional reference to FIGS. 3C and 3D, the block assembly 300 includesa sample block 302 comprising an upper surface 303 and a plurality ofvessel or sample well or receiving elements 304. The receiving elementsmay be disposed within a rectangular area having a long side having adimension “L” and a short side having a dimension “S” that is less thanthe dimension L, for example, when the block 302 is configured toreceive a standard 96-well or 384-well microtiter plate. The sampleblock 302 may comprise a thermal block 305 that is mounted to, and inthermal contact with, the upper portion of sample block 302, which isconfigured to receive a sample holder or carrier. The thermal block 305may comprise one or more elements for heating and/or cooling (notshown), such as thermoelectric elements, one or more thermal or heatsinks, one or more heat exchangers or fins, and/or one or more fans. Thesample block 302 may be disposed in or on a movable support or base 308,which may include a carrier, base, or tray 306 configured to support,hold, or lock the sample block 302. The carrier 306 may be a separatecomponent that is attached to moveable base 308 or may be integrallyformed with moveable base 308..

Still referring to FIGS. 3A-3D, and additional reference to FIGS. 4A and4B, the sample block 302 may be configured to receive a sample holder316. The sample holder 316 in the illustrated embodiment comprises amicrotiter plate including a plurality of reaction sites 317 in the formwells, reaction volume in a fluidics card, through-holes, surfaceindentations or other surface discontinuities, or the like. In otherembodiments, sample holder 316 may comprise one or more linear strips ofreaction sites, a plurality of individual vials, a sample card, amicrofluidics card, a through-hole array, or the like. The reactionssites 317 may alternatively comprise a plurality of through-holes orother formats discussed above herein. In certain embodiments, the blockassembly 300 may also include a cover 800, which may be configured coversample holder 316 and/or to protect and/or provide optical access toreaction sites 317. In the illustrated embodiments, cover 800 is aheated cover 800 that is configured to heat the top of sample holder316, the top of the thermal block 302, and/or a volume above the sampleholder 316 and/or thermal block 302. Alternatively, cover 800 may be anon-heated cover, for example, a cover plate to protect the content ofsample holder 316, a plate with openings to provide optical access toreaction sites 317, and/or a lenslet array configured to focus lightinto or onto the reaction sites 317.

In certain embodiments, the sample block 302 may be located on or in amoveable base 308 configured to move or transport sample block 302 froma location inside the housing 1001 to a position suitable, for examplealong a horizontal axis as illustrated by the double arrow line in FIG.4B. The moveable base 308 may be configured to move or transport sampleblock 302 along with the sample holder 316, when present, from alocation inside the housing 1001 to a location completely or partiallyoutside the housing 1001, for example, for exchanging the sample block302 for a different sample block 302 (e.g., having a different formatand/or reaction site density) and/or for exchanging the sample holder316 for a different sample holder 316 (e.g., having different samples ornumber of reaction sites).

With additional reference to FIGS. 6A and 6B, sample block 302 mayinclude at least one lock member 310, and the carrier, base, or tray 306may include at least one corresponding lock member 312. The lock members310, 312 are preferably configured to engage with each other to preventremoval from the carrier 306. Additionally or alternatively, lockmembers 310, 312 may be configured to register and/or align sample block302 to carrier 306. In the illustrated embodiment, lock member 310comprises a rail member 310 a and a pair of two latch members 310 battached to or integral with rail member 310 a. Alternatively, lockmember 310 may comprises a single latch member 310 b or three or morelatch members 310 b. In the illustrated embodiment, the lock member 312comprises a rail member 312 a and a pair of two latch members 312 battached to or integral with rail member 312 a, wherein each latchmember 312 b is configured to slide over and/or interlock with arespective latch member 310 b. Alternatively, lock member 312 maycomprises a single latch member 312 b or three or more latch members 312b. As seen in the illustrated embodiment, sample block 302 preferablycomprises two lock members 310 located on opposites sides of the sampleblock 302, while carrier 306 comprises two corresponding lock members312 located on opposites sides of carrier 306. In certain embodiments,sample block 302 comprises a single lock member 310 located on one sideof the sample block 302, while carrier 306 comprises a correspondinglock members 312 located on same side of carrier 306. As discussedfurther herein, the lock members 310, 312 may be controlled by acontroller to be in either a locked configuration, for example whensample holder 316 is being exchanged, or unlocked configuration, forexample when the sample block 302 and/or a mating heated cover (e.g.,cover 800) are being exchanged. heated cover 800

The sample holder 316 may additionally comprise a sample holderradio-frequency identification (RFID) tag 318 containing information ordata regarding the sample holder 316, reagents, dyes, or other chemistrycontained in or on the sample holder 316, history of sample holder use,assay parameters or instructions, and/or the like. In certainembodiments, the sample block 302 and/or sample holder 316 comprise asensor 320 and/or 320' in communication with the sample holder RFID tag318. Additionally or alternatively, the sensor 320' may be located onthe thermal block 305.

As seen in FIG. 10B, in some embodiments, system 1000 may optionallyinclude at least one reagent container 1030 comprising a reagentcontainer RFID tag 1032. The content of the reagent container 1030 mayadded to at least some of the reaction sites 317 in preparation toconduct an assay.

FIG. 4A shows a cross-sectional view of the block assembly 300 of FIGS.3A-3B in a closed position or configuration (e.g., withdrawn or engaged)according to an example embodiment. When the block assembly 300 is inthe closed position, the sample block 302 and heated cover 800 are inposition for performing an assay on the sample holder 316. FIG. 4B showsa cross-sectional view of the block assembly 300 in an open position orconfiguration (e.g., extended or disengaged). In certain embodiments,when the block assembly 300 is in the open position, the sample holder316 may be exchanged for a different sample holder 316; however, thesample block 302 remains locked to the carrier 306 and the cover 800 isheld by the cover carrier 710 and remains inside the housing 1001 of thesystem 1000. In an alternative embodiment, when the block assembly 300is in the open position, the sample block 302 and the heated cover 800are disengaged from their respective carriers and, therefore, the sampleholder 316, the sample block 302, and the heated cover 800 are allavailable for exchange. In one embodiment, a driver, actuator, or drivemechanism 402, e.g., in the form of a stepper motor and worm gear, canoperate to drive the movable base 308 and the carrier, base, or tray306, and sample block 302 mounted thereon, to slide back and forthrelative to the support structure 301 by one or more predetermineddistances between the opened and closed positions. A controller may beused to automatically operate the drive mechanism. At least one sensormay be used to detect the position of the block assembly 300 to providefeedback to the drive mechanism 402. In the open position, the sampleblock 302 may be placed onto or removed from the carrier 306, therebyallowing one sample block to be replaced or exchanged for another sampleblock have a different construction and/or configured to accommodate adifferent type of sample holder while the system 1000 is still poweredup (e.g., while power is still being supplied to the current sampleblock 302 and/or the heated cover 800). In the closed position, normaloperations involving the sample block 302 may be carried out.

FIG. 5A shows a cross-sectional view of the block assembly 300 of FIGS.3A-3B having the sample block 302 disengaged with the movable base 308according to an example embodiment. FIG. 5B shows a cross-sectional viewof the block assembly 300 having the sample block 302 engaged with themovable base 308. For example, a driver, actuator, or drive mechanism502, e.g. in the form of a can-stack linear actuator, can drive a firstconnector member 504 (e.g. a female connector) linked to the movablebase 308 back and forth horizontally to engage/disengage with a secondconnector member 506 linked to the sample block 302. When the first andsecond connector members 504, 506 engage with each other, movement ofthe sample block 302 relative to the movable base 308 is prevented orminimised.

To further positionally secure the sample block 302 relative to the baseand prevent dislodgement of the sample block 302 during operation,additional locking features are provided in the example embodiments asdescribed above with reference to FIGS. 3A-D and also shown in FIGS.6A-B. In one implementation, as the drive mechanism 502 (see FIGS.5A-5B) moves the first connector member 504 (see FIGS. 5A-5B) toward thesecond connector member 506 (see FIGS. 5A-5B), the lock members 310, 312engage with each other. Together with the connector members 504, 506,the lock members 310, 312 help to secure the sample block 302 inposition.

FIG. 7 shows a perspective view of an optics module or assembly 700 anda cover carrier 710 according to an example embodiment. The covercarrier 710 and/or the optics assembly 700 may be attached to and/orsupported by the frame 704. An extendable bellow 708 is disposed betweenthe optics assembly 700 and the cover carrier 710. For example, thebellow 708 is connected to the optics assembly 700 at one end and to acover carrier 710 at the other end. A driver, actuator, or drivemechanism 712 is configured to move the cover carrier 710 vertically upand down, as will be described in further details below with referenceto FIGS. 8A-8D.

As the cover carrier 710 is lowered, the bellow 708 extends, and as thecover carrier 710 is raised, the bellow 708 collapses. Bellow 708provides an enclosure between the top of the cover carrier 710 and theoptics module 700 so that when the cover carrier is in the extended,lowered position, the bellow 708 provides optical isolation from staylight from outside sources that might otherwise introduce noise at theoptical sensor during an assay. Advantageously, the bellow 708facilitates the disclosed configuration which allows the heavier sampleblock 302 to be translated in a horizontal axis for placement orexchange of the sample holder and/or sample block, while the lighterheated cover may be translated in an orthogonal axis for engagement inpreparation for and during a run or assay using the system 1000. As seenin FIG. 10A, the frame 704, including the optics assembly 700 and thecover carrier 710 may be attached or mounted to the support structure301 used to hold and transport the thermal block assembly 300. Thisprovides two separate, single-axis translation systems (one fortransporting the thermal block assembly 300 and the other to place thecover 800 over the thermal block assembly 300). It has been found thatthis arrangement provides more accurate alignment of the cover 800 tothe reaction sites 317 of sample holder 316 than a more complex systemcomprising a dual-axis arrangement.

FIGS. 8A-8D show cross-sectional views illustrating an operation of thecover carrier 710 according to an example embodiment. FIGS. 8A-8B showalternative cross-sectional views as the cover carrier 710 is beinglowered onto a heated cover 800 disposed on a block assembly (notshown), such as the block assembly 300 discussed above. In oneimplementation, the cover carrier 710 includes a plurality alignmentpins 802 a, 802 b (typically at least 2 such alignment pins are used) toalign or approximately align the cover carrier 710 with the heated cover800. In particular, the alignment pins 802 a, 802 b help to ensurealignment between a third connector member 804 on the cover carrier 710with a fourth connector member 806 on the heated cover 800. Additionallyor alternatively, alignment pins 802 a, 802 b are used to register oralign a sample block 302 to the cover carrier 710. The certainembodiments, upper portions of align pins 802 a, 802 b are inserted intocorresponding through-holes or cylinders of system 1000 to register oralign the cover carrier 710 and the sample block 302 to the system 1000(e.g., to the optical assembly 700). Connector members 804, 806 mayinclude electrical contact to provide electrical communication and/orpower to heated cover 800. The cover carrier 710 also includes a grippermechanism which includes gripper arms 808 a, 808 b driven by a driver,actuator, or drive mechanism 810. As the cover carrier 710 moves downtowards the heated cover 800, the gripper arms 808 a, 808 b are opened.As seen in FIG. 9B, there are two gripper arms 808 a and two gripperarms 808 b in the illustrated embodiment. In other embodiments there maybe one, three, or more gripper arms 808 a, 808 b.

FIG. 8C shows a cross-sectional view as the cover carrier 710 is incontact with the heated cover 800. At this point, the third connectormember 806 engages with the fourth connector member 808 (not shown inFIG. 8C). Further, the gripper arms 808 a, 808 b are actuated to closeand generate an active clamping force onto the heated cover 800 tosecurely grip the heated cover 800. Accordingly, the heated cover 800 isfully engaged with the cover carrier 710 by way of both the connectormembers 804, 806 and the gripper arms 808 a, 808 b. From this state, thedrive mechanism 712 can move both the cover carrier 710 and the engagedheated cover 800 upward to a raised position as shown in FIG. 8D.

FIGS. 9A-9K show various views of the cover carrier 710, drive mechanism810, and gripper arms 804, 806. Referring to FIGS. 9A-9C, the covercarrier 710 comprise a carrier plate 900 that mates with a top surfaceof the heated cover 800 and the drive mechanism 810, which is configuredto rotate gripper arms 808 through a linkage 905. FIG. 9A shows apartial cross-sectional view of the drive mechanism 810 according to anexample embodiment. The drive mechanism 810 can control movement of thegripper arms 808 a, 808 b via respective linkages, with linkage 905being shown in FIG. 9 . In addition, the drive mechanism can actuate anejection bar 910 to exert a downward force onto and a corresponding part915. The part 915 is connected to the fourth connector member 806.Accordingly, the drive mechanism 810 can disengage the third and fourthconnector members 804, 806 while opening the gripper arms 808 a, 808 bto thereby disengage the heated cover 800 from the cover carrier 710. Incertain embodiments, the carrier plate 900 comprises the ejector bar910, which may be coupled to the carrier plate 900 (e.g., using anadhesive, bolt, fastener, or the like) be part of a unitary structurewith the carrier place 900. Additionally or alternatively, the third andfourth connector members 804, 806 may be disengaged by using the drivermechanism 712, for example, by separating the cover carrier 710 from theheated cover 800, which may be accomplished by lifting the cover carrier710 away from the heated cover 800.

FIGS. 9E-9H illustrate a preferred embodiment of operation of the drivemechanism 810. The mating heated cover 800 is not shown for simplicity.FIG. 9E shows a first configuration of the drive mechanism 810 and covercarrier 710 in which the gripper arms 808 a, 808 b are in a closedposition suitable for holding the heated cover 800, for example, duringan assay or biological test. FIG. 9F show a second configuration of thedrive mechanism 810 and cover carrier 710 in which the drive mechanism810 is lower relative to the axis of rotation of the gripper arms 808 a,808 b. As a result of this relative motion, the gripper arms 808 a, 808b are now in an open position suitable for release of the heated cover800, for example, in preparation for exchanging the heated cover 800and/or the sample block 302 for a different heated cover 800 and/or thesample block 302 (e.g., exchanging the 96 well format heated cover 800and the sample block 302 for a 384 well or 384 array card format heatedcover 800 and the sample block 302). FIG. 9G show a third configurationof the drive mechanism 810 and cover carrier 710 in which the drivemechanism 810 is lowered even further relative to the axis of rotationof the gripper arms 808 a, 808 b. As a result of this relative motion,the gripper arms 808 a, 808 b may now extended beyond the open positionin the second configuration. The movement between the secondconfiguration and the third configuration the actuation of the ejectionbar 910 to exert a downward force so as to disengage the third andfourth connector members 804, 806, as described above.

With further reference to FIG. 9H, it has been discovered that by properdesign of the interface between heated cover 800 and the gripper arms808, the heated cover 800 can be more accurately aligned to the opticalassembly 700. For example, it has been found that a sloped interfaceangle, θ, may be selected to provide a desirable lateral accuracy orrepeatability in the location in X and Y axes of a plane parallel to theupper surface 303. That is, the sample block 302 may be removed from thesystem 1000, then later be placed back into the system 1000, with anaccuracy or repeatability that is within a predetermined range. Forexample, in a preferred embodiment, it has been found that slopedinterface angle, θ, from 30 degrees to 50 degrees provides a lateralaccuracy or repeatability that is less than or equal to 200 micrometers.For an optical system with a 20x demagnification, this is equivalent toan accuracy or repeatability at the imaging sensor of 10 micrometers. Inanother preferred embodiment, it has been found that sloped interfaceangle, θ, from 30 degrees to 50 degrees provides a lateral accuracy orrepeatability that is less than or equal to 100 micrometers.

With further reference to FIGS. 9J-K, it has been discovered thatinitial alignment of cover carrier 710 to the optical assembly 700 andto the block assembly 300 is critical. For example, in certainembodiments, the cover 800 includes a lenslet array that focusesexcitation light or electromagnetic radiation from an excitation sourceinto each reaction site 317 of a sample holder 316. The lateralpositioning of the lenslet array in two axes in a horizontal planedetermine where the focus of each lenslet is positioned within acorresponding reaction region 317. To facilitate initial alignment ofthe lenslet array to the block assembly 300 and/or sample blocks 300,the cover carrier 710 may comprise an upper plate or assembly 920 and alower plate or assembly 925. During installation and/or alignment ofcover carrier 710 into the system 1000, the upper plate 920 may bemounted or fixed to a frame of system 1000 (e.g., to the opticalassembly 700). The lower plate 925, to which the heated cover 800 ismounted or engage with during use, is moveably mounted or attached toupper plate 920. The lower plate 925 may then be moved in a horizontaldirection in one or two axes, for example while a heated cover 800 or asubstitute thereof, to position the lower plate to a location such thatlight or radiation from the excitation source is properly located withinthe wells or reaction sites 317 of a sample holder 316. Once the lensletarray of the heated cover 800 is aligned to the wells or reaction sites317, the lower plate may be locked or fixed to the upper plate.

In certain embodiments, lower plate 925 comprises at least two alignmentpins 930, which are used to register or align a heated cover 800 to thelower plate. As discussed above, upper portions of align pins 802 a, 802b are inserted into corresponding through-holes or cylinders of system1000 to register or align the cover carrier 710 (more specifically theupper plate 920) to the system 1000 (e.g., to the optical assembly 700).Additionally or alternatively, alignment pins 802 a, 802 b are used toregister or align a sample block 302 upper plate 920 and, as aconsequence, to the system 1000. Lower plate 925 are used to adjust thealignment lenslet array of the heated cover 800 to the wells or reactionregions of a sample block 302, as discussed above. In this way, the pins802 a, 802 b are used to approximately align the lenslet array to thewells or reaction regions of the sample block 302 and the adjustablelower plate is used to provide a more accurate or precise alignment ofthe lenslet array to the wells or reaction regions of the sample block302.

The system according to the present teachings can perform automatedoperations to install and replace/remove the sample block 302 and heatedcover 800 as necessary. Some examples are now described with referenceto FIGS. 3-9 .

In one example to install the sample block 302 and heated cover 800, theblock assembly 300 is initially at the open position when a userinitiates the installation sequence. Depending on the configuration, theheated cover 800 may already be placed onto the sample block 302beforehand, or they can be put together in situ. Alignment features canhelp to position the heated cover 800 correctly relative to the sampleblock 302. One or more sensors may also be used to determine thepresence and/or orientation of the heated cover 800 on top of the sampleblock 302. The sample block 302 together with the heated cover 800thereon is then placed into the carrier, base, or tray 306 of the blockassembly 300.

It will be appreciated that the above steps can be performed by a humanoperator, or alternatively, by an articulated arm. In the latter case,the articulated arm may be remotely controlled by a human operator ormay be programmed to perform the tasks autonomously.

Once the system can confirm the presence of the sample block 302 andheated cover 800, the remaining steps of the installation sequence canbe carried out automatically. For example, the drive mechanism 402 (seeFIG. 4A) draws the block assembly 300 to the closed position. There, thedrive mechanism 712 (see FIG. 7 ) moves the cover carrier 710 (see FIG.7 ) down to engage with the heated cover 800. As the gripper arms 808 a,808 b close onto the heated cover 800 and the cover carrier 710 exerts aclamping force onto the heated cover 800 which is mounted on the sampleblock 302, the sample block 302 is effectively immobilised at this time.

While the sample block 302 is held in position, the drive mechanism 502(see FIG. 5A) moves the first connector member 504 to engage with thesecond connector member 506. The same movement causes the lock members310, 312 to engage with each other. As a result, the sample block 302 issecured to the movable base 308.

After the engagement is completed, the drive mechanism 712 moves thecover carrier 710 in engagement with heated cover 800 to a raisedposition, ready for deployment. For example, the operator may start aPCR experiment, and the block assembly 300 may be extended to the openposition for loading a sample holder and then drawn to the closedposition, before the cover carrier 710 is lowered to begin thermalcycling.

In another example to remove the sample block 302 and heated cover 800,the block assembly 300 may is initially at the closed position and theheated cover 800 is at the raised position when the operator initiatesthe removal sequence. The system can automatically operate the drivemechanism 712 to lower the heated cover 800 onto the sample block 302.Once the heated cover 800 is detected to be on top of the sample block302, the gripper arms 808 a, 808 b open to release the heated cover 800.In addition, the drive mechanism 810 (see FIG. 8 ) causes the ejectionbar 910 to exert a downward force to disengage the third and fourthconnector members 804, 806 from each other. The cover carrier 710, afterbeing separated from the heated cover 800, can be drawn to the raisedposition.

Separately, the drive mechanism 502 automatically causes the first andsecond connector members 504, 506 to disengage from each other, and lockmembers 310, 312 to dislodge from each other. Accordingly, the sampleblock 302, having the heated cover 800 on top, is disengaged from themovable base 308, and the drive mechanism 402 can move the sample block302 to the open position where both the sample block 302 and heatedcover 800 can be retrieved/removed, for example, by a human operator oran articulated arm.

As seen in FIG. 3A system 1000 may also include electronic components314, which may include or be part of one or more controllers configuredto control movement and/or engagement of the various components ofsystem 1000. For example, at least some of the electronics components314 may be configured, alone or in conjunction with electronics ofsystems outside housing 1001 in communication with system 1000, tocontrol the motion or engagement of any or all of sample block 302, thecarrier 306, moveable base 308, connector members 504 and/or 506, cover800, connectors 804 and/or 806, lock members 310 and/or 312, gripperarms 808 a, b, cover carrier 710, bellows 708. For example, at leastsome of the electronics components 314 may be configured, alone or inconjunction with electronics of systems outside housing 1001 incommunication with system 1000, to control the motion of the sampleblock 302 and/or movable base 308 relative to support structure 301, asillustrated in FIGS. 4A and 4B. Additionally or alternatively,electronic components 314 may be configured to move cover 800 and/orcover carrier 710 relative to sample holder 316 and/or sample block 302.In certain embodiments, electronic components 314 may be configured tooperate lock members 312 to engage lock members 310 of the sample block302, for example, to secure or lock the sample block 302 to the moveablebase 308 or carrier 306. In certain embodiments, electronic components314 may be configured to secure or lock cover 800 to cover carrier 710,for example, using gripper arms 808 a and/or 808 b, wherein the covercarrier 710 may be used to lift cover 800 off of the sample block 302before moving the sample block outside housing 1001 to exchange oradjust the sample holder 316. Alternatively, the electronic components314 may be configured to disengage

System Integration

In addition to the block assembly 300, optics assembly 700 and covercarrier 710 as described above, the system 1000 also includes a backchassis assembly 1002 which can provide electrical and thermalmanagement for the system 1000. As illustrated in FIGS. 10A and 10B, thehousing 1001 may enclose any or all of block assembly 300, opticsassembly 700, cover carrier 710, and/or back chassis assembly 1002.Housing 1001 may formed by various member that are attached to oneanother, for example members 1004, 1006, 1008, 1010 together with fronthousing 1012 shown in FIG. 10B.

The front housing 1012 also include a drawer face 1014 and a door face1015 disposed above the drawer face. During operation, the drawer facemoves forward when the block assembly moves from the closed position tothe open position. If only a sample holder 316 is to be inserted orexchanged, the door face 1015 remains stationary. If the sample block302 and/or the heated cover 800 are being exchanged, the drawer face1014 moves forward and the door face 1015 is flipped open from the topto allow passage of the heated cover 800. Alternatively, the door face1015 may be raised up and/or retracted into the system 1000 during thisoperation to allow passage of the heated cover 800. As a safety orprecautionary feature, the door face 1015 may be configured to move toan open position (e.g., flipped or raised) during start up of the system1000. This preclude possible damage to the system 1000 if, for example,the block assembly 300 was in an open position during the most recentpower down (either intentionally or accidentally, for example due to apower failure). In this case, no damage to the door face 1015 wouldoccur during retraction of the block assembly 300 back into the housing1001 to a closed position during or after start up of the system, sincethe door face 1015 would be opened or retracted.

The front housing 1012 includes several input/output features. A displayscreen 1016 capable of receiving touch input is mounted on the fronthousing 1012. In one implementation, the front housing 1012 comprises animage system 1017 comprising one or more cameras that may be configuredto detect or identify the face of a perspective user of the system 1000.The image system 1017 may be configured to provide or produce one ormore outputs if one or more predetermined criteria are met, for example,if the face of the perspective user matches that stored data ofindividuals authorized of use the system 1000 and/or have access tocertain capabilities of the instrument or information stored in thesystem 1000 or in a database to which the system 1000 has access. Incertain embodiments, the image system 1017 may comprise a 3-dimensional(3D) camera module 1017. The 3D camera module 1017 is capable ofdetecting facial expressions and body gestures, and may be equipped withfacial recognition software to automatically recognise a face of aregistered user. Additionally or alternatively, the image system 1017may be located at other locations, such as in or one a top or side panelof the system 1000.

Alternatively or in addition, the system 1000 may comprise voice system1018 comprising one or more microphones 1018, for example, mounted onthe front housing 1012. The voice system 1018 may be equipped with voicerecognition software to automatically recognise voice instructions froma registered user.

The system 1000 and/or the front housing 1012 may also have a proximitysensor 1020 to detect an object or individual, e.g. a user, at apredetermined distance to turn on the 3D camera module 1017 and activatethe microphones 1018. The proximity sensor may by any of the proximitysensors, probe, or device known in the art. Accordingly, in some exampleembodiments, it is possible to operate the system 100 in hand-free mode,e.g. by a voice command or body gesture. In certain embodiments, anoutput from the proximity sensor 1012 may be used enable the imagingsystem 1017 and/or the voice system 1018. The proximity sensor 1012 maybe utilized in an environment in which two or more instruments 1000 arelocated in the same in a laboratory or room. Additionally oralternatively, the output from the proximity sensor 1020 may be used todetermine whether output from the imaging system 1017 and/or the voicesystem 1018 will be utilized for starting, powering up, or activatingthe system 1000 and/or allow access to certain capabilities of theinstrument or information stored in the system 1000 or in a database towhich the system 1000 has access.

In this manner, it may be determined which system 1000 a user havingaccess to the two or more instruments 1000 is to respond to a voicecommand or a face recognition signal. For example, if the user providesa voice command to activate or start one of the instruments 1000, or toimplement some function of the system 1000, only the system 1000 towhich the user is in closest proximity will respond. In certainembodiments, several authorized uses may be in the same laboratory orroom, and each system 1000 will respond to each user in accordance totheir proximity to a respective one of the instruments. It isanticipated that such capabilities may be utilized in other types ofbiological analysis instruments or non-biological analysis instrumentshaving capabilities and features different from those disclosed herein,but having a proximity sensor 1020 according to the embodimentsdiscussed herein used in the manner just described.

A pair of speakers 1022 may also be mounted to the front housing 1012 toprovide audio updates, warnings, etc. such that a human operator doesnot need to regularly look at the display screen 1016.

The system 1000 may also include several features to further enhanceperformance. With reference to FIGS. 3C, 3D and 6A, the block assembly300 further includes at least one ejector member 600 configured to atleast partially raise the sample holder 316 away from the sample block302 when in the open position. This can prevent the sample holder fromsticking to the sample block 302 (as is the case in some existingsystems) and facilitate removal of the sample holder from the sampleblock 302 after an experiment, especially when the removal is performedby an articulated arm (i.e. a robot). The inventors discovered thatmanual and/or robotic removal of sample holder 316 is better facilitatedwhen ejector members 600 are located along the long side for the sampleholder 316 corresponding to the L dimension in FIG. 3 , rather than onthe short side corresponding to the S dimension. For example, after aPCR assay using the system 1000, the edges of the sample holder 316 bowdownward toward the center. It has been discovered that the depth of thebowing is greater on the long side that the short side of the sampleholder 316. By placing the ejector members 600 along the long sidecorresponding to the L dimension in FIG. 3C, the clearance between theedge of the sample holder 316 and the surface 303 of the sample block302 is greater than when the ejector members 600 are place on the shortside corresponding to the S dimension in FIG. 3C. This may be accountedsince the depth of the bowing is less along the short side of the sampleholder 316 and may also be account for in that the greater bowing on thelong side will tend to project the sample holder 316 further away fromthe surface 303.

FIG. 11A shows a cross-sectional view illustrating an improved seal inthe form of a double lip seal 1100 attached to a lower surface of theheated cover 800. FIG. 11B shows a magnified view of the seal 1100. Thedouble lip design of the seal 1100 can avoid flaring issues, andcorresponding poor sealing issues, occurring existing system using priorart single edge or single blade seals. These prior art single bladedesigns have been found to induce higher pressure in the four corners ofthe seal during compression when heated cover 800 in down position. As aconsequence, sealing degrades over time and repeated use. The disclosedthe double lip seal 1100 is configured to provide even contact with thesurface 303 of sample block 302, thereby reducing or minimizing heatloss/interference to or from the external environment. In addition toproviding a superior sealing at the surface 303, the bellows formed bythe double lip seal also provides additional insulating properties ofthe seal itself, since the air between the inner and outer walls of theseal provided additional insulation.

The system 1000 according to the present teachings is also capable ofboth detecting a presence of a sample holder on the sample block 302,and reading relevant information about the sample holder. For example,as the cover carrier 710 is lowered together with the heated cover 800onto the sample block 302 before an experiment run, the actual height ofthe heated cover 800 is monitored via feedback from one or moreencoders. The height of the heated cover 800 is greater when the sampleholder is present than when the sample holder is absence, due to thethickness of the sample holder. Accordingly, the presence or absence ofthe sample holder can then be determined. In certain embodiments, one ormore such encoders may be used to distinguish between different typesand/or brands of sample holder has been located within the sample block302 based on differences in thickness between different types or brands.Similarly, the encoder(s) may be used to determine whether a correct orpreferred sample holder has been located within the sample block 302.

Referring to FIGS. 3C, 3D, and 12 , the system 1000 may include firstand second RFID antennas 1200 a, 1200 b in communication with respectivefirst and second devices 1202 a, 1202 b. The devices 1202 a, 1202 b maybe an RFID reader, RFID writer, or combination RFID reader/writer. Incertain embodiments, devices 1202 a, 1202 b may be combined into asingle device that communicates with both antennas 1200 a, 1200 b.Devices 1202 a, 1202 b, alone or in combination with system 1000 and/oranother system in communication with system 1000, may be configured toread RFID tag 318. The RFID tag 318 and the data contained therein maybe used to confirm presence of the RFID, confirm the correct sampleholder is being used, perform a pre-run check prior to performance of anassay using system 1000, control the system 1000 and/or assays run onsystem 1000 (e.g., by providing information about sample holder 316and/or reaction sites 317 to generate a protocol for use by system 1000to run an assay, experiment, or test on sample holder 316). In someembodiments, devices 1202 a and/or 1202 b may be configured to writedata generated during an assay conducted on the system 1000.Additionally, data recorded on RFID tag 318 during the assay and/or dataalready contained on the RFID tag prior to placement in the system 1000may be used to process the data produced during the assay.

After the run, the RFID writers/readers 1202 a, 1202 b can writeinformation onto the sample holder RFID tag to mark the sample holder asused which can prevent the sample holder from being re-run. Theinformation can also be transmitted to a remote location, e.g. forinventory control and procurement purposes. The 2 readers also allowdetection of the orientation of the sample holder. If a user place doesnot place the sample holder in normal orientation, system software canaccount for the angular offset for display and analysis.

Referring to FIG. 13 , in certain embodiments, a method 1300 forperforming a biological analysis in an automated fashion withoutintervention or any further input needed by a user after initialinstructions have been sent to begin an assay. The inventors have foundthat method 1300 produces unexpected advantages over current practicesin which a user must either manually input assay protocolinformation/instructions into a system for running an assay (e.g., bylooking in a database by cross referencing a sample holder ID) and/orhaving obtaining assay protocol information/instructions by connectingto network such as a LAN or cloud database. These current practices arenot only time consuming, but are less secure, since proprietaryinformation resides at and/or is sent to sites that are remote from theinstrument performing the assay. In many applications, it is criticalthat input and/or output data related to the assay be maintained in asecure environment to protect from unauthorized access to such data.Using embodiment of the current teaching, all input necessary toconfigure an assay protocol remains local with sample holder and sampleholder RFID tag. In addition, sample holder RFID tags according toembodiments of the present teaching may be used configured to receiveinformation related to output from the assay run, such as run parametersand conditions and/or data generated during the assay run.

The method 1300 may be used in conjunction with the sample holder RFIDtag and/or reagent container RFID tag, for example, the sample holderRFID tag 318 and/or reagent container RFID tag 1032. When no reagentcontainer RFID tag is present or being utilized, the method 1300includes an element 1310 comprising placing a sample holder (e.g.,sample holder 316) into or onto a biological analysis system (e.g.,system 1000) and an element 1320 comprising receiving from a user aninitial user input to initiate an assay. In some embodiments, theinitial input from the user may also initiate transport and/orpositioning of a sample holder, as discussed above herein regardingmovement of sample block 302/ thermal block 305 after placement of asample holder into carrier, base, or tray 306.

The method 1300 also includes an element 1330 comprising reading atleast some of the RFID data using one or more antennas associated withthe sample holder RFID tag, for example, one or both RFID antennas 1200a, 1200 b. The method 1300 further includes element 1340 comprisinggenerating instructions to perform an assay based at least in part onthe read RFID data. After receiving the initial user input, the method1300 additionally includes an element 1350 comprising executing a set ofsteps to perform an assay on the sample holder without any further inputor intervention from the user until the assay is completed. The set ofsteps may comprise or be provided by a protocol, which may be configuredat least in part from data contained on the sample holder RFID tag.Optionally, additional input to an assay protocol after the initial userinput, for example, to further customize the protocol.

In certain embodiments of the method 1300, one or more reagentcontainers each have their own RFID tag may be included in the system1000 (e.g., reagent container 1030 and reagent container RFID tag 1032).In such embodiments, the method 1300 may also include an element 1360comprising reading information from the reagent container RFID tag forone or more of the reagent containers. The method 1300 then includes anyor all of the elements 1310 to 1350..

Referring to FIG. 14 , in certain embodiments, a method 1400 forperforming a biological analysis is utilized to determine an orientationof a sample holder within a system or instrument, for example, theorientation of the sample holder 316 within the sample block 302.Advantageously, this allows the sample holder in some embodiments to beloaded without having to orient the sample holder be matched to a key.Additionally or alternatively, this may allow the same sample block(e.g., sample block 302) to be compatible with different types of sampleholders, such as different types of plates or with various plates havingdifferent form features (e.g., to be compatible with both 96 wellmicrotiter plates and 4, 8, or 12 well strips).

Using the system 1000 as an example, the method 1400 includes an element1410 comprising placing the sample holder 316 in or on the sample block302. The method 1400 also comprises elements 1420 and 1430 comprisingdetermining if RFID data from sample holder RFID tag 318 is beingdetected from either or both RFID antennas 1200 a, 1200 b. if no RFIDdata is received by either antenna 1200 a, 1200 b, the method 1400includes element 1440 of generating either (1) producing or generating asignal indicative that the sample holder 316 does not contain an RFIDtag or (2) producing or generating a signal indicative that no sampleholder is present. If other means, either active or passive, are usedfor determining the presence of the sample holder 316, then the systemwould be configured to utilize the second option. Additionally oralternatively, the system may be configured to produce or generate anuncertainty signal if the possibility of a faulty RFID tag is suspected(e.g., based on an antenna signal that is ambiguous or if other meansexists for validating the presence of an RFID tag on the sample holder).

Optionally, the method 1400 may include an element 1450 comprising, ifRFI D data is received by one of the RFID antennas, then generating atleast one of (1) a signal indicative that the sample holder 302 containsa sample holder RFID 318 or (2) a signal indicative of an orientation ofthe sample holder 316. In certain embodiments, the inventors havediscovered that detection of the orientation is accomplished byconfiguring the antennas 1200 a, 1200 b, the sample holder 316, and theRFID tag 318 so that when the sample holder 316 is oriented as shown inFIGS. 3C, 3D, the signal from the RFID tag 318 is strong enough to bereceived by antenna 1200 a, but the signal to antenna 1200 b is too weakto be received. Conversely, if the sample holder 316 is rotated 180degrees from that shown in FIGS. 3C, 3D, then the signal from the RFIDtag 318 is strong enough to be received by antenna 1200 b, but thesignal to antenna 1200 a is too weak to be received. In this manner, theorientation of the sample holder 316 can be detected based on the signalor lack of signal in antennas 1200 a, 1200 b. Additionally oralternatively, a single RFID device 1202 a or b, and/or a single RFIDantenna 1200 a or b, may be used to determine the orientation of sampleholder 316 based on the strength of the signal received from the RFIDtag 318.

The inventors have discovered that there is an advantage in separatingthe antennas 1200 a, 1200 b from the RFID devices 1202 a, 1202 b. Incertain embodiments, communication between antennas 1200 a, 1200 b andRFID devices 1202 a, 1202 b is provided by a wire between each antennaand the corresponding RFID device. By separating in this way, theinventors have found that the relatively small antennas 1200 a, 1200 b(compared to devices 1202 a, 1202 b) can be placed above the sampleholder 316 and/or sample block 302 so that a relatively week signal fromRFID tag can be received by the antenna that is closer to the RFID tag.

Optionally, the method 1400 may include an element 1460 comprising, ifRFID data is received by both of the RFID antennas 1200 a, 1200 b, thangenerating (1) a signal indicative that the sample holder 316 containstwo sample holder RFID tags 318 or (2) a signal indicative that twosample holders 316with sample the holder RFID tag 318 are present.

In certain embodiments, a method 1500 of using an instrument or system(e.g., the system 1000) comprises an element 1510 including querying anactivation and/or recognition system to produce a first output, theactivation and/or recognition system comprising one or more of a voiceactivation and/or recognition system or a face activation and/orrecognition system. For example, the activation and/or recognitionsystem may comprise the image system 1017 and/or the voice system 1018discussed above herein.

The method 1500 further comprises an element 1520 including determiningwhether the first output meets one or more first predetermined criteria.

The method 1500 further comprises an element 1530 including querying aproximity sensor to produce a second output. For example, the proximitysensor may comprise the proximity sensor 1020 discussed above herein.

The method 1500 further comprises an element 1540 including determiningwhether the second output meets one or more second predeterminedcriteria.

The method 1500 further comprises an element 1550 including starting,powering up, activating, or otherwise using a capability or data of theinstrument if both (1) the first output meets the one or more firstpredetermined criteria and (2) the second output meets one or moresecond predetermined criteria.

In certain embodiments, the method 1500 of using the instrument comprisea method of starting, powering up, or activating the instrument and/or amethod of utilizing or initiating certain capabilities of the instrumentor of utilizing or granting access to information stored in the systemor in a database to which the instrument has access.

It will be appreciated by a person skilled in the art that numerousvariations and/or modifications may be made to the present disclosure asshown in the specific embodiments without departing from the scope ofthe present disclosure as broadly described. The present embodimentsare, therefore, to be considered in all respects to be illustrative andnot restrictive.

1-102. (canceled)
 103. A biological analysis system comprising: ahousing; a sample block disposed within the housing and configured toreceive a sample holder comprising a sample holder RFID tag; a firstRFID antenna configured during use to receive RFID data from the sampleholder RFID tag; and an RFID reader configured to receive the RFID datafrom the first RFID antenna; wherein the first RFID antenna is spatiallyseparated from the RFID reader.
 104. The biological analysis system asin claim 103, further comprising: a second RFID antenna, the second RFIDantenna configured during use to receive the RFID data from the sampleholder RFID tag; wherein the RFID reader is configured to receive theRFID data from the second RFID antenna.
 105. The biological analysissystem as in claim 104, further comprising at least one RFID writerconfigured to write data on the sample holder RFID tag.
 106. Thebiological analysis system of claim 104, wherein the system comprisesthe sample holder and the sample holder RFID tag.
 107. The biologicalanalysis system as in claim 106, wherein: sample holder comprises aplurality of spatially separated reaction locations, each of theplurality of spatially separated reaction locations comprising aplurality of characteristics; the sample holder RFID tag includes RFIDdata comprising data for the plurality of characteristics each of thereaction location; wherein the RFID data comprises at least 8 kilobytes,at least 64 kilobytes, or at least 128 kilobytes.
 108. The biologicalanalysis system of claim 106, wherein the RFID writer is configured towrite assay information generated during an assay onto the sample holderRFID tag.
 109. The biological analysis system of claim 108, wherein thesystem is configured to use the assay information to analyze dataobtained during the assay.
 110. The biological analysis system of claim106, wherein the plurality of characteristics comprises one or more ofa: sample holder ID; sample holder expiration date; sample holder partnumber; sample holder barcode; sample holder lot number; sample holdertype; sales order number; EDT file format; EDF file format; or internetlinks or addresses.
 111. The biological analysis system of claim 106,wherein the plurality of characteristics comprises one or more of a:storage temperature and/or storage temperature range; sampleconcentration; sample concentration recommended range; assay name(s)and/or locations on sample holder; assay IDs; suggested protocol orrequired protocol; sample name; master mix name; master mix change; dyename; suggested or required filter or set of filters to be used duringan assay on the sample holder; passive reference dye; reaction volume;target name; dye name; sample name; analysis settings; flag setting;sample type; or target type.
 112. The biological analysis system ofclaim 106, wherein the plurality of characteristics comprises one ormore of a: run protocol comprising one or more of a heated covertemperature, reaction volume, temperature step value, temperature stagevalue; or well information for one or more wells, the informationincluding one or more of target name, dye name, or sample name; reagentname.
 113. The biological analysis system of claim 106, wherein the RFIDdata on the sample holder RFID include re-writeable data comprising oneor more of a: passive reference dye; reaction volume; target name; dyename; sample name; analysis settings; flag setting; sample type; targettype; run protocol comprising one or more of a heated cover temperature,reaction volume, temperature step value, temperature stage value; orwell information for one or more wells, the information including one ormore of target name, dye name, or sample name; reagent name.
 114. Amethod for performing a biological analysis using the biologicalanalysis system of claim 104, the method comprising: placing the sampleholder into or onto the biological analysis system; receiving from auser an initial user input to initiate an assay; reading at least someof the RFID data using the first RFID antenna; generating instructionsto perform an assay based at least in part on the read RFID data; (1)after receiving the initial user input, executing a set of steps toperform an assay on the sample holder without any further input orintervention from the user until the assay is completed or (2) receivingadditional input and then executing a set of steps to perform an assayon the sample holder without any further input or intervention from theuser until the assay is completed.
 115. The method as in claim 114,further comprising: providing a reagent container comprising a reagentcontainer RFID tag; reading information from the reagent container RFIDtag; and based at least in part on the information read from the reagentcontainer RFID tag, generating the assay protocol.
 116. A method forperforming a biological analysis using the biological analysis system ofclaim 103, wherein the system comprises as second RFID antenna, themethod further comprising: placing the sample holder in or on the sampleblock; verify whether at least one of the first RFID antenna or thesecond RFID antenna is(are) receiving RFID data or signal from thesample holder; performing at least one of: if no RFID data is receivedby either the first RFID antenna or the second RFID antenna, generating(1) a signal indicative that the sample holder does not contain an RFIDtag and/or (2) a signal indicative that no sample holder is present; ifRFID data is received by at least one of the RFID antennas, generatingat least one of (1) a signal indicative that the sample holder containsa sample holder RFID tag and/or (2) a signal indicative of anorientation of the sample holder; and if RFID data is received by bothof the RFID antennas, generating (1) a signal indicative that the sampleholder contains two sample holder RFID tags and/or (2) a signalindicative that two sample holders with sample a holder RFID tag arepresent.
 117. The biological analysis system as in claim 103, wherein anorientation of the sample holder is based on the strength of the data orsignal from the RFID tag.
 118. A biological analysis instrumentcomprising: a proximity sensor configured determine the presence ordistance of a perspective user of the instrument; an activation and/orrecognition system comprising at least one of a voice activation and/orrecognition system or a face activation and/or recognition system; aprocessor and a memory coupled to the processor, the memory includinginstructions to: query the activation and/or recognition system toproduce a first output; determine whether the first output meets one ormore first predetermined criteria; query the proximity sensor to producea second output; determine whether the second output meets one or moresecond predetermined criteria; and start, power up, or activate theinstrument if both (1) the first output meets the one or more firstpredetermined criteria and (2) the second output meets one or moresecond predetermined criteria.
 119. A method of starting, powering up,or activating the biological analysis instrument of claim 118, themethod comprising: querying the activation and/or recognition system toproduce the first output; determining whether the first output meets theone or more first predetermined criteria; querying a proximity sensor toproduce a second output; determining whether the second output meets theone or more second predetermined criteria; starting, powering up, oractivating the instrument if both (1) the first output meets the one ormore first predetermined criteria and (2) the second output meets one ormore second predetermined criteria.